Class#9-EtOH Flashcards
EtOH effects?
disinhibition/relaxation (stimulation at low level), sedation, hypnosis, general anaestesia, coma, death
CNS depressants 5 majors concepts?
- Additive effects: add to one another
- Can’t reverse with stimulants
- General depressants are not totally general
- Chronic use ->rebound effect
- Cross-tolerance: tolerance to one will be tolerant to another
Higher [] =
more widespread effect
Amnesia types?
- Partial: Universal, dose related
2. Blackouts: NO memory, susceptibility varies
Level of BAC driving impairment starts at?
0.03%
Etoh effect on cortex, hippocampus/cerebellum
judgment, memory and coordination
EtOH effets on receptors/dynamics (8)?
- GABA a (major inhibitory): opens channel and maximize Cl- crossing. Affect subsynaptic and postsynaptic receptor + extra synaptic receptors for GABA inducing tonic inhibition = substained inhibition of a neuron. Can also increase release of presynaptic GABA.
- Release glycine and enhance postsynaptic 1 response (inhibitory pathway). Mainly in spinal cord (coordination) and brainsteam (resp/cardiac functions),. Pathway coupled to ion channel through GPCR
- Decrease excitatory. Block glutamate transmission by blocking NMDA receptors (impaired intellectual functions). Chronic use upregulate GluN1 and GluN2B. This contribute to EtOH tolerance.
- Block release of Ach = amnesia/cognitive impairments
- Decrease serotonin = impulsivness and aggression
- Facilitate release of dopamine in reward pathway, lead to addiction
- Facilitate release of endorphins - addiction
- Blocks voltage-operated calcium channels (VOCC) = reduce neurotransmitter release
Effect on kidneys.
decrease reabsorption = increase excretion
Absorption?
- Highly lipid soluble and readily absorbed. If drink rapidly rate of absorption increase and rate of metabolism decrease.
- 20% in stomach, 80% in SI
- If gastric emptying rate higher = higher absorption rate. Carbonation.
- Emptying rate decreased by food, particularly lipid
- Peak BAC level lower when stomach full then empty
Metabolism?
- 20% in stomach mucosa by ADH (lower in women)
- Low dose first order kinetics (1/2 drink per hours), high dose zero order kinetics.
- Alcohol Dehydrogenase (ADH) -> acetyldehyde, then Acetyldehyde Dehydrogenase (ALDH) -> Acetate
Distribution
- Goes everywhere. AVD = to total body water. More [] in women b/c less water%.
- Easily BBB
- Can stimulate directly vomiting center in medula and CTZ
Elimination
10%: breath, urine, sweat
10%: MIcrosomal enz. P450
80%: ADH in cytosol
ADH molecule?
Dimer with 6 potential subunits
ALDH subtypes? most important?
9, ALDH2
chronic etoh P450?
- Chronic use: CYP2E1
Etoh therapeutic index
4
Liver diseases?
Hepatitis - reversible
Fatty liver -reversible
Fibrosis- irr.
Cirrhosis - irr.
#Also affect vasc. in SI = lower blood flow to liver
#Hepatic encephalopathy: liver cannot metabolize
Tolerance
Acute:
Chronic: More NMDA, more metabolism, behavioral
Disulfiram?
Block ALDH = flushing, headaches, nausea, vomiting, hypotension
